Benzothiazole-, benzoxazole- and benzimidazole-2-thioacrylates and process



b a/a BENZOTETHIAZGLE, BENZQXAZOLE- AND EENZ- IMiDAZLE-2=THEQACRYLATESAND PRQCELlS Lee A. Miller, Dayton, Ohio, assigns-r to Monsanto Chemicaltlonipany, St. Louis, Mo., a corporation of Delaware No Drawing. FiledDec. 28, 1959, Ser. No. $62 .lli

12 Claims. (Cl. 26ti3l6) ZOECCOOY in which X is selected from the classconsisting of -S, -O and NH-, Y is an alkyl radical of from 1 to 5carbon atoms, and Z is selected from the class consisting of Y, hydrogenand aryl radicals of from 6 to carbon atoms.

The presently provided compounds are thus alkyl esters of acrylic acidwherein at the 3-position of the acrylic acid there is carried asubstituent which is a benzothiazoylthio radical, or a benzoxazolylthioradical or a benzirnidazolylthio radical and wherein the 3-position mayor may not carry an alkyl or aryl substituent. Thus when Z of the aboveformula is hydrogen the compounds are alkyl3-(2-benzothiazolylthi0)acrylates, or 3-(2-benzoxazolylthio acrylates or3- (2-benzirnidazolylthio acrylates.

The mercapto-substituted polynuclear heterocyclic compounds which arepresently employed are Z-mercaptobenzothiazole, Z-benzoxazolethiol or2-benzimidazolethiol.

The acetylenic carboxylates which are reacted with the abovemercapto-substituted compounds are 1 to 5 C alkyl esters of propiolicacid wherein there may or may not be present at the 3-position of thepropiolic acid an aliphatic or aromatic substituent. Examples of thepresent useful acetylenic esters are the alkyl propiolates such as themethyl, ethyl, propyl, isopropyl, butyl, tert-butyl, isobutyl, amyl,isoamyl, or tert-amyl propiolates; the alkyl tetrolates such as themethyl, ethyl, propyl, butyl or amyl tetrolates; the alkyl Z-pentynoatessuch as the methyl or butyl Z-pentyonate or the ethyl or isopropyl4-ethyl 2- pentynoate, the alkyl Z-hexynoates such as methyl or propylZ-hexynoate; the arylpropiolates such as ethyl or amyl phenylpropiolateor 2-, 3-, or 4-tolylpropiolate and methyl or butyl wnaphthylpropiolate;the alkyl Z-heptynoates such as ethyl or butyl Z-heptynoate or methyl,ethyl or isobutyl 6-methyl 2-heptynoate; the alkyl 2-octynoates such asmethyl or propyl 2-octynoate, etc.

Examples of compounds prepared according to the presently providedprocess are, e.g., methyl, ethyl, amyl 3-(2-benzothiazolylthio)acrylate,ethyl, propyl or butyl (Z-benzoxazolylthio)acrylate; butyl, isoamyl, ormethyl 3-(2-benzimidazolylthio)acrylate; methyl or ethyl 3-(2-benzothiazolylthio)-2-butenoate; methyl or butyl 3-(2-benzoxazolylthio)-2-butenoate; butyl or amyl 3-(2-benz- 3,0h8,239Patented Dec. Il, 1962 imidazolylthio)-2-butenoate; methyl or ethyl3-(2-benzothiazolylthio)-2-pentenoate, butyl or methyl3-(2-benzoxazolylthio)-2-buter1oate, amyl or butyl3-(2-benzimidazolylthio)-2-pentenoate, methyl or ethyl3-(2-benzoxazolylthio)-2-pentenoate, amyl or isopropyl3-(2-benzothiazolylthio)-2-hexenoate, ethyl or methylS-(Z-benzoxazolylthio)-2-hexenoate, amyl or methyl3-(2-benzimidazolylthio)-2-hexencate, methyl or ethyl3-(2-benzothiazolylthio)-2-heptenoate, butyl or isopropyl 3-(2-benzoxazolylthio)-2-heptenoate, butyl or propyl3-(2-benzothiazolylthio)-2 octenoate, methyl or ethylS-(Z-benzoxazolylthio)-2-octenoate, methyl or ethyl 3-(2-benzothiazolylthio) 3 -phenylacrylate, ethyl or isopropyl 3 (2-benzoxaz olylthio)-3-phenylacrylate, methyl or butyl 3-(2-benzothiazolylthio)-3-(2-tolyl)acrylate, ethyl or propyl 3-(Z-benzothiazolylthio -3- (4-ethylphenyl) acryl ate, methyl or ethyl3-(2-benzothiazolylthio)-3-(;3-naphthyl) acrylate, ethyl or propyl3-(2-benzoxazolylthio)-3-(ot-naphthyl)- acrylate, butyl or methyl3-(2-benzimidazolylthio)-3-(B- naphthyl)acrylate, etc.

Reaction of the present mercapto-substituted polynuclear heterocycliccompounds with the acetylenic esters takes place in the presence orabsence of basic or acidic catalysts. Basic catalysts useful in theprocess include organic bases such as pyridine, the quaternary ammoniumsalts or bases such as trimethylbenzylammonium hydroxide, the alkali andalkali metal hydroxides or basically reacting salts thereof such assodium, potassium, lithium, calcium, or magnesium hydroxide, carbonatesor acetate; alkali or alkali metal alcoholates such as sodium methylate,etc. Examples of useful acidic catalysts are acid reacting metallicsalts, such as cuprous or cupric, stannous or stannic, ferrous or ferricacetates, sulfates or chlorides, organic or inorganic acids such asacetic, sulfuric, phosphoric or oxalic acid, etc. While I prefer to useas a catalyst a material which is soluble in the mixture of the tworeactants such solubility of the catalyst in the reactants is not anecessary property of the catalyst.

According to the invention the presently provided heterocyclicthioalkenoates are readily prepared by simply mixing the mercaptocompound with the acetylenic ester in the presence or absence of eitherthe acidic or basic catalyst and in the presence or absence of an inertdiluent or solvent and allowing the resulting reaction mixture to standat ordinary or increased temperatures until formation of the substitutedolefinic ester has occurred. Useful solvents or diluents are e.g.,benzene, xylene, dioxane, dichlorobenzene or hexane. Depending on thenature of the individual reactants and of the catalyst employed, thereaction may occur under varying conditions of temperature and pressure.For optimum yields, it is advantageous to heat the reaction mixture attemperature of, say, from approximately 60 C. to the refluxingtemperature of the reaction mixture.

Inasmuch as molecular equivalents of the mercapto compound and theacetylenic ester are involved in the formation of the presently providedsubstituted olefinic esters, it is advantageous to employ stoichiometricproportions of the two reactants. If desired, however, any excess ofeither reactant may be employed since any unreacted material is readilyseparated from the product.

It has been observed that in the reactions with the 2-benzimidazolethiol, the product is generally a mixture of the isomericalkyl 3-,(2-benzimidazolylthio)alkenoates.

aeeaaas and the alkyl 3-[l-(2-mercaptobenzimidazole)]acrylates It willbe noted that (11) is formed by addition of the acetylenic ester at theimino radical of the thiol rather than at the mercapto radical. There isa preferental tendency for (I); so that (II) is present in minoramounts. While (11) may be removed from the reacton mixture by customaryisolating procedures, e.g., close fractional distillation, extraction orfractional crystallization, for most purposes it is unnecessary toprovide (1) in a pure form. That it is because the crude (I), i.e., thereaction product which consists essentially of (I), is useful directlyfor a wide variety of industrial and agricultural purposes.

The presently provided alkyl 3-(2-benzothiazoylthio)- alkenoates or3-(2-benzoxazolylthio)ialkenoates or the 3-(Z-benzimidazolylthioalkenoates and mixtures of the latter with theisomeric alkyl 3[1-(Z-mercaptobenzimidazole)1- acrylates are stable,rather high-boiling viscous liquids or waxy to crystalline solids whichare useful as lubricant additives, as vulcanization accelerators forrubbers, as copolymerizing monomers with vinyl compounds in syntheticresin and plastics manufacture, and as biological toxicants, e.g., asherbicides, bacteriostats, fungistats and insecticides. They areparticularly valuable as pre-emergent herbicides in that they possess aspecificity of effect so that they can be used as de-weeders withoutadversely affecting the crop. The benzothiazolylthio compounds arenoteworthy in that they serve as crab grass eradicants without killingor substantially injuring the lawn grasses.

The invention is further illustrated by, but not limited to, thefollowing examples:

a eaeeer 'JSH Example 1 A mixture consisting of 8.4 g. (0.1 mole) ofmethyl propiolate and 50 ml. of benzene was added continuously to amixture consisting of 16.7 g. (0.1 mole) of 2-mercaptobenzothiazole, 100ml. of benzene and 1 ml. of 40% methanolic trimethylbenzylammoniummethoxide. The reaction mixture, which darkened immediately, was heatedat reflux for 12 hours. It was then dissolved in 100 ml. of ether andwashed with two 50 ml. portions of saturated aqueous ammonium chloride.Evaporation of the organic solvents gave as residue a brown slurry. Thiswas distilled through a small Vigreux column to give the substantiallypure methyl 3-(2-benzothiazolylthio)- acrylate, B.P. 171-172 C./0.5 mm.,M1. 68-70 C., which analyzed 52.51% carbon and 3.60% hydrogen as against52.56% and 3.61%, the respective calculated values.

Example 2 To a reaction vessel there were charged 15.0 g. (0.1 mole) of2-benzimidazolethiol, 9.2 g. (0.11 mole) of methyl propiolate and 100ml. of benzene. Upon addition of 1 ml. of trimethylbenzylammoniumhydroxide (catalyst) to the mixture, darkening was noted and thetemperature of the reaction mixture rose exotherrnally to about 45 C. Inorder to assure complete reaction the whole was then refluxed for 12hours. At the end of that time the black reaction mixture was evaporatedto give a dark brown, pasty solid which could not be recrystallized frommethanol. Diflicul-ty in crystallization 4 was due to the presence in aproduct of the following two isomers:

amount of (II), i.e., methyl 3-[l-(Z-mercaptobenzimida- Zole) acrylate.

and

CSH

Example 3 When a catalytic quantity (1 ml.) of trimethyl-benzylammoniumhydroxide was added to a mixture consisting of 15.1 g. (0.1 mole) of 2-benzoxazolethiol, 9.2 g. (0.11 mole) of methyl pro-piola-te and ml. ofbenzene, the mixture blackened and spontaneously warmed to 45 C. Thewhole was then heated at reflux for 12 hours. Upon evaporation of thesolvent there was obtained a black oil which solidified upon standing.Repeated recrystallization from methanol gave the substantially puremethyl 3-(2-benzoxazo1ylthio) acrylate, buff needles, M.P. 93.5- 95.0"C., which analyzed 56.14% carbon and 4.10% hydrogen as against 56.16%and 3.86% the respective calculated values for C H NO S. Infraredanalysis showed the presence of the -C=N structure at 1590 cmf thepresence of C-O- ester structure at 1230 and 1220 cmf and the presenceof 4 adjacent protons at 755 and 750 CDT-1.

Example 4 This example shows evaluation of the methyl3-(2-benzothiazolylthio)acrylate of Example 1 as a pre-emergentherbicide. Briefly, the chemical is applied in spray form to soil seededto representative grasses and broad-leaf plants.

Aluminum pans, 13" x 9" x 2", were filled with a good grade of top soilwhich had been screened through a A" wire mesh and mixed with sand in apreparation of two parts of the top soil to one part of the sand. Thesoil surface was then compacted to a depth of from the top of the pan.Twenty seeds each of morning glory, wild oat, crab grass, rye grass,radish, sugar beet, barnyard grass, wild buckwheat, and pigweed werethen scattered on the soil surface and covered with soil to the pan top.

The present herbicidal solution was prepared by dissolving 0.4 g. of themethyl 3-(2-benzothiazolylthio)-- acrylate in 20 cc. of acetone. Ten ml.of this solution was diluted with water to 30 cc. Application of thisquantity of the solution to said pans is calculated to correspond to theuse of 25 lbs. of the test compound per acre. The planted pans were thenplaced in an exhaust hood and sprayed first with 30 cc. of an aqueoussolution of a liquid fertilizer and 0.1% solution of octamethylpyrophosphoramide. The liquid fertilizer was employed to give a uniformnutrition level and the amide was employed to prevent insect injury. Twopans were then respectively sprayed with the 25 lb. per acre solutionofthe test compound. One of the pans which had been planted and treatedwith the liquid fertilizer and octamethyl pyrophosphoramide in the samemanner was set aside to be used as a blank. The three pans were thenplaced in /2 of water and allowed to absorb moisture through perforatedbottoms until the soil surface was completely moist. The pans were thentransferred to a wet sand bench in the greenhouse, and maintained therefor ten days under ordinary conditions of sunlight and watering.

Observation of the pans at the end of that time showed that those whichhad been sprayed with the 25 lb. per acre solution of the methyl3-(2-benzothiazolylthio)- acrylate showed complete to very pronouncedsuppression of crab grass and pigweecl; however, the radish, morningglory, wild buckwheat, wild oats, rye grass and barnyard grass hademerged and showed no evidence of phytotoxicity. Also, all of the typesof seeds which had been planted in the pan which had not been sprayedwith the methyl 3-(2-benzothiazolylthio)acrylate had emerged and theplants were in excellent condition. Accordingly, when used at the rateof 25 lbs. per acre, the methyl 3-(2-benzothiazolylthio)acrylate is anunusually effective preemergent herbicide in that it prevents emergenceand growth of crab grass and pigweed without having any adverse effecton wild oats, rye grass, and mustard.

Employing the same testing procedure, but using morning glory, wild oat,brome grass, rye grass, radish, sugar beet, foxtail, crab grass,pigweed, soybean, wild buckwheat, tomato and sorghum as the test seeds,the methyl 3-(2-benzoxazolylthio)acrylate of Example 3 was also found togive complete to very pronounced suppression of crab grass and pigweed.However, with this compound there was not the pronounced specificitywhich was exhibited by the methyl 3-(2-benzothiazolythio) acrylate; forin addition, wild oat and rye grasses were pronouncedly suppressed bromegrass and sugar beets were moderately injured, and morning glory,foxtail, and soybean were slightly injured. There was no effect onradish, wild buckwheat, tomato and sorghum. Accordingly, the methyl3-(2-benzoxazolylthio)acrylate is a preemergent herbicide which iseffective against the narrow leafed plants, generally, while notsubstantially harming the broad leaf plants.

When employing the same testing procedure with the product of Example 2,i.e., the mixture of methyl 3-(2- benzimidazolylthio)-acrylate andmethyl 3-[1-(2-mercaptobenzimida2ole)] acrylate completely differentresults were obtained. This product was found to inhibit germination andgrowth of several broadleaf plants, e.g., morning glory, sugar beets andtomato, while not at all affecting wild oat, brome grass, rye grass,foxtail, and crab grass.

Example 5 This example shows evaluation of the methyl3-(2-benzothiazolylthio)acrylate of Example 1 and the methyl 3-(Z-benzoxazolylthio)acrylate of Example 3 against mosquito larvae. Thefollowing procedure was employed:

Culture tubes (rimless, 25x200 mm.) were respectively filled with 70 cc.of distilled water. Acetone solutions (1.0%) of the test compounds werethen respectively pipetted ipto the culture tubes in a quantitycalculated to give a p.p.m. concentration of either the compound ofExample 1 or the compound of Example 3 in each of said tubes. Each tubewas rubber-stoppered and shaken vigorously to facilitate completemixing. To each tube of the resulting test solutions there was thenadded approximately 25 yellow fever mosquito (Aedes aegypti Linne)larvae, and the test solutions, with their larvae content, were allowedto stand for 24 hours at room temperature. Observation of the tubes oflarvae at the end of that time showed 100% kill of larvae in the tubescontaining either the compound of Example 1 or the compound of Example3.

Example '6 This example describes testing of the methyl 3-(2-benzothiazolylthio) acrylate of Example 1 against Monilim'a fructicola,the causal agent of brown rot of stone fruits. The following procedurewas used:

A spore suspension of the organism was prepared from a 7 day old culturethereof on a slant of an agar culture medium by removing said sporeswith a rubber policeman from the slant and suspending them in distilledwater. The concentration of spores was adjusted to about 40,000 per ml.of Water. The test compound was added to water in a concentrationcalculated to give 50 parts of the compound per million parts of Water.An 0.02 ml. aliquot of each of the resulting solutions was pipettedrespectively into duplicate wells of a depressed glass slide and al:lowed to evaporate to dryness. Then an 0.1 ml. aliquot of the abovespore suspension was pipetted into each well. The concentration of thetest compound in each well was thus lowered to 10 parts per millionparts of diluent. The slides were then incubated in a moist chamber for18 hours at 25 C. Inspection of the slides at the end of this timeshowed no germination of spores in the presence of the 10 ppm.concentration of the test compound, i.e., on the slides in which saidmethyl 3-(2-benzothiazolylthio)acrylate had been deposited; whereasthere was profuse spore germination on controls, i.e., on slides inwhich none of said compound had been deposited.

Example 7 This example shows testing of the methyl3-(2-benzothiazolylthio)acrylate of Example 1 against the fungusAspergilln's niger. The following procedure was used:

An inoculum preparation of Aspergillus niger SN-lll was prepared byadding 10 ml. of sterile distilled Water to a 7-day old, Sabourardsdextrose agar slant culture thereof anddislodging the spores into thewater with a transfer needle.

Culture media was prepared by respectively adding 18 ml. of Sabourardsdextrose agar to 18x150 mm. straight side test tubes, capping with metalculture tube caps, and sterilizing in an autoclave for fifteen minutesat 121 C.

A stock solution of the test compound was prepared by respectivelydissolving mg. of said test compound in 10 ml. of acetone: at 1% acetonesolution of the compound was thus obtained.

Using a sterile 5 ml. pipette, 2 m1. of said 1% solution was transferredto a tube of melted, sterile culture media prepared as described above.A dilution of 1 part of test compound per 1,000 parts of agar resulted.This was further diluted with additional sterile agar to give a 100 ppm.concentration of the test compound in the agar. The thus-diluted agarwas then poured into sterile Petri dishes and allowed to harden.

The four plates of agar were then respectively inoculated with one dropof the above-described inoculum preparation. Examination of the platesafter a five-day incubation period showed no growth of the Aspergillusniger at the 100 ppm. concentration of the methylS-(Z-benzothiazolylthio acrylate.

Example 8 give an 0.1% (1000 ppm.) concentration of the test compound inthe agar. The 0.1% agar solution of the test compound was then pouredinto a Petri dish and allowed to harden. This plate was inoculated withboth the Staphylococcus aureus and the Salmonella typhosa, and incubatedfor two days at 37 C. At the end of that time, inspection of the plateshowed no growth of either organism on the plate which contained the0.1% concentration of the test compound.

The present compositions are characterized by a high degree of efiicacyin that even in very low concentration,

e.g., in a concentration of as low as one p.p.m. they may be extremelyeffective against bacteria and fungi. Biological toxicant compositionscontaining the present compounds are advantageously obtained by firstpreparing a solution thereof in an organic solvent and then adding theresulting solution to water containing an emulsifying agent to form anoil-in-water emulsion. Because of their efiectiveness, they are presentin the toxicant compositions in only very small concentrations, forexample in concentrations of from 0.0001 percent to 1.0 percent byweight of the total weight of the emulsion. Emulsifying agents which maybe employed are those customarily used in the art for the preparation ofoil-in-water emulsions. Examples of emulsifying agents which may be usedinclude alkylbenzenesulfonates, long chained polyalkylene glycols, longchained alkylsulfosuccinate, etc.

While the present compounds are most advantageously employed asbiological toXicants by incorporating them into an emulsion as hereindescribed, they may also be incorporated into solid carriers such asclay, talc, pumice or bentonite to give compositions which may beapplied either to infested areas or to locale which may be subject toinfestation. They may also be dissolved in liquefied gases such as thefluorochloroethanes or methyl chloride and applied from aerosol bombscontaining the solution.

Biological compositions and methods employing the present heterocyclicesters are claimed in my copending, divisional applications Serial No.197,838, filed May 28, 1962, and Serial No. 197,855, filed May 28, 1962.

What I claim is:

1. A compound of the formula in which X is selected from the classconsisting of -S-, O and -NH-, in which Y is alkyl of from 1 to 5 carbonatoms, and Z is selected from the class consisting of Y, hydrogen andhydrocarbon aryl of from 6 to 10 carbon atoms.

2. A compound of the formula in which Y is alkyl of from 1 to 5 carbonatoms.

3. A compound of the formula o-s-on=onooov in which Y is alkyl of from 1to carbon atoms.

4. A compound of the formula in which Y is alkyl of from 1 to 5 carbonatoms.

5. Methyl 3-(Z-benzothiazolylthio)acrylate.

6. Methyl 3-(2-benzimidazolylthio)acrylate.

7. Methyl 3-(2-benzoxazolylthio)acrylate.

8. The method of preparing sulfur-containing, heterocyclic olefinicesters which comprises contacting an acetylenic ester of the formulaZCECCOOY in which Z is selected from the class consisting of hydrogen,alkyl of from 1 to 5 carbon atoms and hydrocarbon aryl of from 6 to 10carbon atoms with a mercapto-substituted heterocyclic compound of theformula C-SH where X is selected from the class consisting of --S-, -O-and -NH.

9. The method of preparing alkyl esters of heterocyclicsulfur-containing acrylates which comprises contacting an alkylpropiolate having from 1 to 5 carbon atoms in the alkyl radical with acompound of the formula gs-.. X/

where X is selected from the class consisting of -S, -O-- and NH.

10. The method of preparing methyl 3-(2-benzothiazolylthio) acrylatewhich comprises contacting methylpropiolate with2-mercapto-benzothiazole in the presence of a basic catalyst and aninert diluent.

11. The method of making methyl 3-(2-benzimidazolylthio)acrylate whichcomprises contacting methyl propiolate with 2-benzimidazolethiol in thepresence of a basic catalyst and an inert diluent.

12. The method of preparing methyl 3-(2-benzoxazolylthio)acrylate whichcomprises contacting methyl propiolate with Z-benzoxazolethiol in thepresence of a basic catalyst and an inert diluent.

References Cited in the file of this patent UNITED STATES PATENTS2,468,075 Jayne et al Apr. 26, 1949 2,535,876 Stewart Dec. 26, 19502,647,877 Dazzi Aug. 4, 1953 2,776,977 DAmico Jan. 8, 1957 2,819,965Murray et al Jan. 14, 1958 2,861,918 Kosrnin Nov. 25, 1958

1. A COMPOUND OF THE FORMULA
 2. A COMPOUND OF THE FORMULA